Suppression of R5-type of HIV-1 in CD4+ NKT cells by Vδ1+ T cells activated by flavonoid glycosides, hesperidin and linarin

Abstract

We established transfectants expressing T cell receptors (TCRs) either for Vγ1 and Vδ1 (1C116) or for Vγ2 and Vδ2 (2C21) using the TCR-deficient Jurkat T cell line J.RT3-T3.5. The amount of IL-2 secreted from these γδ T cell clones accurately indicated TCR-dependent stimulation. Clone 2C21 was specifically stimulated by previously reported ligands for Vγ2Vδ2 (Vδ2)-TCR such as isopentenyl pyrophospate (IPP), ethylamine, or risedronate. In contrast, clone 1C116 was strongly stimulated through the Vγ1Vδ1 (Vδ1)-TCR by flavonoid glycosides such as hesperidin and linarin, having both rutinose at the A ring and methoxy (-OCH3) substitution at the B ring. Additionally, hesperidin and linarin showed stimulatory activity for peripheral blood mononuclear cell (PBMC)-derived T cells expressing Vδ1-TCR; these activated Vδ1 + T cells also secreted IL-5, IL-13, MIP-1α, MIP-1β and RANTES. Such PBMC-derived Vδ1 + T cells stimulated by hesperidin and linarin suppressed R5-HIV-1-NL(AD8) viral replication in CD4 + NKT cells in a dose-dependent manner. To the best of our knowledge, this is the first demonstration that flavonoid glycosides activate functional Vδ1 + T cells.

Flavonoids as Promising Antiviral Agents against SARS-CoV-2 Infection: A Mechanistic Review

“…Furthermore, methoxy (-OCH3) substitution at the B ring is essential for the stimulatory activity of hesperidin and linarin on CD4+ NKT cells. They could also induce RANTES, MIP-1α, and MIP-1β secretion from Vδ1+ expressing T cell receptors which subsequently suppressed viral replication in CD4+ NKT cells [ 104 ]. Kang et al reported anti-influenza effects of purified flavonoids from Pithecellobium clypearia Benth on the in vitro model of influenza A virus infection.…”

Linarin Protects the Kidney against Ischemia/Reperfusion Injury <i>via</i> the Inhibition of Bioactive ETS2/IL-12

“…As an extract of C. indicum, LIN has been widely studied in different medicinal fields. 19,20) The effective use of LIN for anti-IRI therapy was demonstrated based on research on cardiac disease. 13) In the current study based on the IR model, we found that LIN could also protect kidney from IRI and inhibit the upregulation of IL-12 p40 induced by IR.…”

A Multidisciplinary Approach to Coronavirus Disease (COVID-19)

“…Again, baicalin and baicalein (baicalin aglycon; selectivity index (SI): 19 µM and 118 µM) inhibited 3CL pro with a potency close to CQ (EC 50 : 1.13 µM and SI: 88.61 µM) in the in vitro test and fluorescence resonance energy transfer protease test on Vero E6 cells contaminated with SARS-CoV-2 [324]. In a study in China where detailed analysis of all proteins encoded by SARS-CoV-2 genes was performed, it was suggested that hesperidin could prevent the virus from entering the cell because it overlaps significantly with the ACE2 interface [325]. It has been noted that caffeic acid, the strongest phenolic bioactive component in the structure of Sambucus formosana Nakai, with many biologic potentials including antiviral activity, blocks the adhesion of HCoV-NL63 to the cell surface regardless of the cell type used [323].…”